Circulating angiopoietin-2 is a strong prognostic factor in acute myeloid leukemia

Abstract

Angiogenesis plays an important role in solid tumors and hematologic malignancies. The angiopoietins act as essential regulators in this process. We investigated the impact of circulating angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2) and soluble Tie2 (sTie2) on overall survival in patients with acute myeloid leukemia (AML). Ang-1, Ang-2 and sTie2 were measured in plasma samples from 68 AML patients and 11 controls using enzyme-linked immunosorbent assay. Circulating levels of Ang-2 and sTie2 (median (range): 1098.0 (361.4-4147.6) pg/ml and 3.40 (1.21-10.00) ng/ml, respectively) were significantly elevated in AML patients as compared to controls (307.9 (199.7-1225.0) pg/ml and 2.88 (1.71-3.29) ng/ml; Po0.001 and P ¼ 0.014). In a univariate Cox proportional hazards model, higher levels of Ang-2 and sTie2 were predictive of poor survival. In multivariate analyses, Ang-2 and cytogenetics proved to be independent prognostic factors, with a relative risk of 4.07 (95% confidence interval (CI) 1.88-8.81) and 2.70 (95% CI 1.25-5.81), respectively. The 3-year survival rate for AML patients with Ang-2 levelsX1495.6 pg/ml was only 14.7% compared to 64.7% for those with Ang-2 levelso1495.6 pg/ml. These data provide evidence that circulating Ang-2 represents an independent prognostic factor in AML and may be used as a prognostic tool in the risk-adapted management of AML.

Prognostic value of soluble angiopoietin-2 and soluble Tie-2 in Egyptian patients with acute myeloid leukemia

“…Our findings are in line with a recent observation of elevated Ang-2 and Tie-2 levels in patients with chronic myeloid leukemia (CML) and multiple myeloma [14]. It was found that blood levels of sAng-2 and sTie-2 were strongly associated with the extent of BM infiltration, TLC and LDH, providing indirect evidence that the leukemic blasts themselves at least significantly contributed to the plasma levels of the tested angiogenic factors [19]. Furthermore, a strong correlation could be demonstrated between plasma levels of Ang-2 and Tie-2 and the overall survival in AML patients after chemotherapy.…”

“…In fact, it is entirely possible that a predominant proportion of circulating Ang-2 could be secreted by activated BM endothelial cells, given the increased angiogenic activity in the leukemic BM. Furthermore, it is conceivable that Ang-2 could also be released by the endothelium of the normal vasculature upon dysregulated stimulation by leukemic blasts [19]. Our findings are in line with a recent observation of elevated Ang-2 and Tie-2 levels in patients with chronic myeloid leukemia (CML) and multiple myeloma [14].…”

“…The expanded endothelial microenvironment is able to support leukemic cell survival and growth by secretion of hematopoietic growth factors [18]. Moreover, angiogenic mediators produced by AML cells also act through external and internal autocrine loops, thereby directly promoting cell survival, proliferation and disease progression independently from the mechanisms of angiogenesis [19].…”

Serum angiopoietin-1 as a prognostic marker in resected early stage lung cancer

“…There are a few studies on serum Ang-1 levels, and these have reported conflicting results. Compared with the level in controls, the serum Ang-1 level was elevated in breast cancer [25] but lower in thyroid cancer [26]; the level was similar to the control level in prostate cancer [25] and acute myeloid leukemia [27].…”

“…The tissue expression level of Ang-2 is related to the stage progression and overall survival [23,24]. Serum Ang-2 has also been reported to be increased in breast cancer [25], prostate cancer [25], thyroid cancer [26], acute myeloid leukemia [27], and lung cancer [28], with prognostic implications in the latter two cancers.…”